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Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.
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Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.
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Linfocitos Infiltrantes de Tumor , Terapia Neoadyuvante , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Persona de Mediana Edad , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Resultado del Tratamiento , Anciano , Supervivencia sin EnfermedadRESUMEN
Endocervical adenocarcinoma (ECA), harboring poor prognosis, is divided into human papilloma virus (HPV)-associated adenocarcinoma (HPVA) and non-HPVA (NHPVA), each consisting of a heterogeneous immune microenvironment. We aim to examine the effect of CKLF-like MARVEL transmembrane domain 6 (CMTM6), a key regulator of PD-L1, on ECA. Immunohistochemistry and RNA-sequencing (RNA-seq) were used to detect CMTM6, Programmed death ligand 1 (PD-L1), and immune cells biomarkers levels in tumors. RT-qPCR and Western Blotting were used to detect the mRNA and protein level changed in cells. The expression of CMTM6 in ECA is upregulated compared to cervical squamous cell carcinoma tissues. More infiltrating T cells were observed in CMTM6high ECA tissues, especially in CMTM6high HPVA. Higher expression of CMTM6 is associated with a higher rate of infiltrating CD8+ T cells in HPVA, but not in NHPVA. ECA patients were divided into three groups according to the co-expression status of CMTM6 and PD-L1(CPS) . Patients with CMTM6high /PD-L1(CPS+) had the longest OS and DFS, especially in NHPVA patients. Moreover, knock down of CMTM6 promotes ECA cell proliferation via the p53 pathway. CMTM6 recruits T cells, suppresses ECA cell proliferation via the p53 pathway and can be used as a novel prognostic indicator for ECA patients.
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Adenocarcinoma , Neoplasias del Cuello Uterino , Femenino , Humanos , Antígeno B7-H1/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/análisis , Linfocitos T CD8-positivos , Proliferación Celular , Microambiente TumoralRESUMEN
OBJECTIVE: To compare and analyze the early clinical outcomes of unicompartmental knee arthroplasty with mobile and fixed platform for the treatment of single compartment osteoarthritis of knee. METHODS: From January 2013 to December 2014, 86 cases (92 knees) of knee osteoarthritis with single compartment (medial) were randomly divided into two groups. One group consisted of 42 patients, including 18 males and 24 females, underwent unicompartmental knee arthroplasty with fixed platform prosthesis; the other group consisted of 44 patients, including 20 males and 24 females, underwent unicompartmental knee arthroplasty with mobile platform prosthesis. The surgery was performed by the same group of doctors. The operation time, blood loss, ROM, KSS and HSS scores of knee joint before and after surgery were recorded and the clinical follow up was completed. RESULTS: The follow-up duration of the two groups ranged from 8 to 26 months, with an average of (18.20± 4.23) months. During the follow-up period, the periprosthetic fracture was found in 1 patient in the fixed platform group 1 year after operation, and polyethylene liner dislocation was found in 1 patient in the mobile platform group. No complications such as poor wound healing, periprosthetic infection or sterile prothesis loosening were found in all cases. In the fixed platform group, the operation time was (90.05±6.59) minutes and the blood loss was (53.76±6.04) ml. In the mobile platform group, the operation time was (90.73±6.74) minutes and the blood loss was (54.34±6.27) ml. In the fixed platform group, the ROM of knee increased from preoperative (94.52±4.54) degree to postoperative (104.64±4.42) degree. In the mobile platform group, the ROM of knee increased from preoperative (95.05±4.87) degree to postoperative (105.07±4.33) degree. In the fixed platform group, the KSS score increased from preoperative 48.69±5.68 to postoperative 83.55±5.37. In the mobile platform group, the KSS score increased from preoperative 49.39±5.68 to postoperative 84.11±6.14. In the fixed platform group, the HSS score increased from preoperative 45.45±3.62 to postoperative 84.55±6.08. In the mobile platform group, the HSS score increased from preoperative 45.93±4.01 to postoperative 85.16±6.30. There was no significant difference between the two groups. CONCLUSION: There is no significant difference in the early outcome of unicondylar prosthesis with fixed and mobile platforms in the treatment of single compartmental osteoarthritis of knee. The long-term complications and revision rates of the two prostheses need further multi center and large-sample clinical study.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Estudios de Casos y Controles , Femenino , Humanos , Articulación de la Rodilla , Masculino , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The HSulf-1 gene is an important factor that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix, resulting in disturbance of HSPG-related signal transduction pathways. Recently, HSulf-1 has been reported to be down-regulated in several human cancers. In this study, we first cloned and characterized the 5' promoter region of the HSulf-1 gene (around 400 bp) that contained high basal promoter activity. We also found that this functional promoter region was hypermethylated in a number of human cancer cell lines. Furthermore, we found that hypermethylation in this promoter region correlated with the down-regulation of the HSulf-1 expression in human breast and gastric cancer cell lines and tissue samples. These results suggest that the promoter hypermethylation may be one of the mechanisms of the HSulf-1 gene silencing in human breast and gastric cancers. Finally, we demonstrated that the HSulf-1 promoter was more frequently (p<0.05) methylated in cell-free DNA extracted from serum samples of human breast and gastric cancer patients than that of healthy people (76.2%, 55.0% and 19.0%, respectively), indicating that detection of the HSulf-1 promoter methylation in serum samples may have clinical implications in early detection and diagnosis of human breast and gastric cancers.
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Neoplasias de la Mama/genética , Metilación de ADN/genética , Silenciador del Gen , Regiones Promotoras Genéticas , Neoplasias Gástricas/genética , Sulfotransferasas/genética , Adulto , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TransfecciónRESUMEN
ACTX-8 is a protein isolated from Agkistrodon acutus snake venom in our laboratory. It demonstrates cytotoxic activity on various carcinoma cell lines in vitro. However, the mechanism by which ACTX-8 inhibits cell proliferation remains poorly understood. In this study the influence of ACTX-8 on the activation of apoptotic pathway in Hela cells was investigated. We demonstrated that cell death induced by ACTX-8 was concentration- and time-dependent. Apoptotic changes such as phosphatidyl serine externalization and DNA fragmentation were detected in ACTX-8-treated cells. Caspase activation and reactive oxygen species (ROS) production were involved in ACTX-8-induced apoptosis, but pan caspase inhibitor, z-VAD-fmk, could not inhibit cell death induced by ACTX-8 completely, which proved the existence of another pathway for ACTX-8-induced cell death. We found cytochrome c release into cytosol and mitochondrial membrane potential (MMP) dissipation in ACTX-8-treated cells, which indicated that mitochondrial pathway played a role in ACTX-8-induced cell apoptosis. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was not changed by ACTX-8 treatment. However Bad and Bax were translocated from cytosol into mitochondria, and the coimmunoprecipitation result indicated that in mitochondria Bak and Bcl-xL dissociation was followed by the binding of Bad and Bcl-xL. Taken together, the study indicated mitochondrial pathway played an important role in the ACTX-8-induced apoptosis, which was regulated by Bcl-2 family members.
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Agkistrodon , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Venenos de Crotálidos/química , Neoplasias del Cuello Uterino/patología , Animales , Caspasa 3/biosíntesis , Caspasa 9/biosíntesis , Inhibidores de Caspasas , Fraccionamiento Celular , Supervivencia Celular/efectos de los fármacos , Venenos de Crotálidos/farmacología , Citocromos c/metabolismo , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Activación Enzimática , Inhibidores Enzimáticos/farmacología , Femenino , Células HeLa/patología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosfatidilserinas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
Using the rhizome of Curcuma xanthorrhiza Roxb. as explant to induce the adventitious bud, multiplication and radication. The results showed that the inducing and differentiating of bud was better on MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, the multiplication of bud was on MS+6-BA 1.2 mg/L + NAA 0.l mg/L and the redication was on 1/2 MS + NAA 0.5 mg/L.
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Curcuma/crecimiento & desarrollo , Plantas Medicinales/crecimiento & desarrollo , Medios de Cultivo/química , Medios de Cultivo/farmacología , Reguladores del Crecimiento de las Plantas/farmacología , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo , Rizoma/efectos de los fármacos , Rizoma/crecimiento & desarrollo , Técnicas de Cultivo de Tejidos/métodosRESUMEN
To analyze the biological effects of the space environment, we flew nine lines of rice seeds on the Chinese 20(th) recoverable satellite for a duration of 18 days. The same lines of seeds were also irradiated to low doses (2.0 mGy) of Carbon, or Neon or Iron ions (with different LET value of 13.3 keV/microm, 31 keV/microm and 500 keV/microm respectively) at National Institute of Radiological Sciences in Chiba, Japan. The total number of mitotic cells and chromosomal aberrations were analyzed. The mitotic index (MI) and the frequency of chromosomal aberration were evaluated in order to compare the cytogenetic damages from spaceflight and from exposure to similar doses of charged particle on the ground. The results of the present study show that the space environment and heavy energy ion can alter cell growth, and induce various chromosome aberrations including micronuclei, chromosomal bridges, fragments and laggards. With all the lines combined, the frequency of chromosome aberrations and MI in seeds flown in space are the highest. The effectiveness of cytogenetic damage from spaceflight (SP) and the heavy ion irradiations is SP > Fe > Ne > C.
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Aberraciones Cromosómicas , Cromosomas de las Plantas/efectos de la radiación , Iones Pesados , Oryza/efectos de la radiación , Semillas/efectos de la radiación , Vuelo Espacial , Adaptación Fisiológica/fisiología , Adaptación Fisiológica/efectos de la radiación , Análisis Citogenético , Relación Dosis-Respuesta en la Radiación , Oryza/genética , Dosis de Radiación , Semillas/genéticaRESUMEN
AIM: To explore the effects of peptide S-8300 from shark liver (S-8300) on liver function as well as in regulating immune functions in experimental injury models. METHODS: Mice were administered with different doses of S-8300 for four consecutive days, followed by mice injected with tetrachloromethane (CCl(4)) on d 3. The activity of ALT, AST, LDH, SOD and contents of MDA and GSH in the mice liver were tested. And mice were treated with Cy (100 mg/kg) at the beginning of the experiment to induce immunosuppression model. The S-8300 groups were treated with S-8300 seven days after the beginning of Cy administration. The effects of S-8300 on the formulation of serum hemolysin and the content of IL-2 in serum in the immunosuppression mice were observed. RESULTS: S-8300 obviously decreased the level of ALT (52.2+/-11.0 U/dL vs 135.9+/-6.5 U/dL, P<0.01), AST (67.5+/-6.9 U/dL vs 238.8+/-8.7 U/dL, P<0.01), LDH (155.1+/-46.8 U/dL vs 240.4+/-6.0 U/dL, P<0.01) and MDA (0.64+/-0.027 nmol/mg vs 1.06+/-0.040 nmol/mg, P<0.01) and increased SOD (24.51+/-1.01 U/mg vs 19.05+/-0.73 U/mg, P<0.01) and GSH (24.17+/-0.91 microg/mg vs 14.93+/-0.45 microg/mg, P<0.01) in mice liver damaged by CCl(4). S-8300 also markedly improved the formulation of serum hemolysin (0.094+/-0.005 A(540) vs 0.063+/-0.006 A(540), P<0.01) and increased the level of IL-2 (9.74+/-1.16 pg/mL vs 5.81+/-0.87 pg/mL, P<0.01) in serum of the immunosuppression mice. CONCLUSION: The results suggested S-8300 has significant hepatoprotective, immunomodulatory and inhibiting of lipid peroxidation activity.
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Factores Inmunológicos/farmacología , Hepatopatías/tratamiento farmacológico , Péptidos/farmacología , Tiburones , Animales , Cobayas , Sistema Inmunológico/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado , Hepatopatías/inmunología , Hepatopatías/patología , Ratones , Ratones Endogámicos ICRRESUMEN
OBJECTIVE: To evaluate the value of laminar flow in the treatment of burns. METHODS: The air in the laminar flow chamber and the wound tissues of the patients were sampled for bacterial detection. The number and stains of bacterial colony from different classes of laminar air flow chambers at different time points were inspected and compared. RESULTS: The bacterial number was 0 in the laminar flow chamber of 1000 grade, which was obviously different from that in the public area. The mortality was obviously decreased in the laminar air flow chamber with shorter treatment time and hospitalization. No wound infection occurred and the wounds healed smoothly in all these patients. CONCLUSION: The application of laminar air flow can be helpful for the treatment of severe burns.
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Bacterias/aislamiento & purificación , Quemaduras/terapia , Ambiente Controlado , Ventilación , Movimientos del Aire , Recuento de Colonia Microbiana , Monitoreo del Ambiente , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To evaluate the clinical efficacy of low molecular weight heparin (Fraxiparine) in rescuing venous crisis of island skin flap. METHODS: Of the 73 patients with venous crisis of island skin flap, 47 received subcutaneous injection of low-molecular-weight heparin (group I) and 26 were treated with phlebotomy, local compression and topical application of unfractionated heparin solution gauze (group II). RESULTS: The flap survival ratio was (88.46∓8.64)% in group I and (38.37∓6.53)% in group II (P<0.001). At 0, 2, and 4 h after injection of low-molecular-weight heparin, the activated partial thromboplastin time (APTT) was obviously delayed (24.28∓6.71, 41.35∓7.64 and 32.34∓6.35, respectively, P<0.01), FXa:C level was significantly decreased (152.4∓30.7, 65.8∓24.4 and 83.4∓18.4, respectively, P<0.01), while FIIa:C level underwent no obvious alterations (155.70∓31.61, 143.20∓24.75, and 143.4∓23.35, respectively, P=NS). CONCLUSION: Fraxiparine has good antithrombotic efficacy in rescuing venous crisis of island skin flap without adverse effect on systemic coagulation.
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Nadroparina/uso terapéutico , Colgajos Quirúrgicos/efectos adversos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To establish a rat model of full-thickness skin defect to receive bone marrow mesenchymal stem cell transplantation for wound repair. METHODS: A full-thickness skin defect measuring 4 cmx4 cm in 36 F344 rats, which were divided into 3 groups with the wound covered with alloskin graft, acellular dermal matrix, or petrolatum gauze. In vitro cultured BMSCs in the 5th passage were transplanted into the skin defect, and the time of wound dressing dissociation and number of transplanted Brdu-positive cells in the wound were observed 14 days later. RESULTS: The alloskin graft resulted in significantly longer time before dressing dissociation, with greater number of Brdu-positive cells in the wound than the other two wound dressings (P<0.001). The acellular dermal matrix showed better effect than petrolatum gauze in terms of the dressing dissociation time and the viable transplanted cell number in the wound. CONCLUSION: Alloskin graft can be ideal for covering the wound surface to protect the transplanted BMSCs in rats.
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Trasplante de Células Madre Mesenquimatosas , Piel/lesiones , Cicatrización de Heridas , Animales , Células de la Médula Ósea/citología , Dermis/trasplante , Femenino , Masculino , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Ratas Wistar , Trasplante Homólogo , Cicatrización de Heridas/fisiologíaRESUMEN
In present paper, the properties of molecular authentication combined with the fingerprints of high performance liquid chromatography (HPLC) were validated by analyzing ten batches of Fructus Evodiae samples (the dried nearly ripe fruit of Evodia rutaecarpa (JUSS.) BENTH., Evodia rutaecarpa (JUSS.) BENTH. var. officinalis (DODE) HUANG or Evodia rutaecarpa (JUSS.) BENTH. var. bodinieri (DODE) HUANG). The results of this investigation show that the similarities of internal transcribed spacer (ITS) sequences were almost 100% in Evodia rutaecarpa (JUSS.) BENTH. var. bodinieri (DODE) HUANG, 97% in Evodia rutaecarpa (JUSS.) BENTH., and 96% in Evodia rutaecarpa (JUSS.) BENTH. var. officinalis (DODE) HUANG. The percentage of identity between the two groups of Evodia rutaecarpa (JUSS.) BENTH. var. bodinieri (DODE) HUANG and Evodia rutaecarpa (JUSS.) BENTH. var. officinalis (DODE) HUANG is almost 96%, but the identity among the group of these three species is only 73%. The results show that Fructus Evodiae comes from three species respectively. The fingerprints of HPLC show that Fructus Evodiae revealed 20 major common peaks. And the three species have almost the same chemical constituents. ITS sequence fingerprint combining the fingerprint of HPLC can not only be developed to identify and distinguish the three species in detail, but also can be used for optimizing location where Fructus Evodiae has much higher bioactive constituents and yield.
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Evodia/química , Cromatografía Líquida de Alta Presión , Dermatoglifia del ADN , ADN de Plantas/química , ADN de Plantas/genética , Evodia/genética , Alcaloides Indólicos/análisis , Control de Calidad , Quinazolinas/análisis , Especificidad de la EspecieRESUMEN
Genetic load in the genome of the model species, rice, was genetically dissected by mapping quantitative trait loci (QTLs) affecting the radiosensitivity of 226 recombinant inbred lines (RILs) to gamma-ray- and spaceflight-induced radiation. The parents and RILs varied considerably in their radiosensitivity to gamma-ray irradiation. A total of 28 QTLs affecting the two index traits, seedling height (SH) and seed fertility (SF), of radiosensitivity were identified. The japonica parent, Lemont, was much more sensitive to gamma-ray irradiation than the indica parent, Teqing, and its alleles at almost all QTLs were associated with increased radiosensitivity, suggesting a much higher genetic load in the japonica genome of rice. Six QTLs (QSh2a, QSh2b, QSh5a, QSh7, QSf3b, and QSf10b) were located in the genomic regions particularly sensitive to radiation and thus might represent possible 'mutation hot spots' in the japonica genome. Detailed characterization of these genomic regions may shed light on the evolution and subspecific differentiation of rice.
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Genoma de Planta , Oryza/genética , Sitios de Carácter Cuantitativo , Evolución Biológica , Mapeo Cromosómico , Rayos gamma , Ligamiento Genético , Endogamia , Oryza/anatomía & histología , Oryza/efectos de la radiación , Infertilidad Vegetal/genética , Infertilidad Vegetal/efectos de la radiaciónRESUMEN
BACKGROUND & OBJECTIVE: Recent studies indicated that heat shock proteins (HSPs) are associated with antigenic peptides and participate in the antitumor T cell response in animals. This study was designed to investigate the mechanism of anti-tumor effect of immune competent cells (ICC) induced by HSP-70 of HeLa (cervical carcinoma) cells in vitro. METHODS: The normal peripheral blood mononuclear cells(PBMCs) stimulated with HSP-70 of HeLa cells in vitro. T cell phenotypes were analyzed before and after stimulated by PBMCs. HSP-70 primed the immune competent cells (ICCs) from PBMCs were tested for cytotoxic activity against HeLa cell. RESULTS: CD3+ cell was 85.73 +/- 1.44%, up from 57.68 +/- 1.46% before the amplification(P < 0.002). CD8+ cell was 48.06 +/- 1.66%, up from 23.56 +/- 1.86% before the amplification(P < 0.002). The ICCs induced by HSP-70 were shown significant cytotoxic activity (82.69 +/- 1.97%, 62.11 +/- 1.61%) against HeLa cells and cervical carcinoma cells, and the cytotoxic activity (31.05 +/- 2.09%) of the ICC against HeLa cells could be blocked by anti-HSP-70 antibody. CONCLUSION: The ICC can be induced selectively by PBMCs with HSP-70 of HeLa cells, and has specific cytotoxic activity against HeLa cell.